Variant 3-170480891-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_020949.3(SLC7A14):c.1391G>C(p.Cys464Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C464F) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC7A14
NM_020949.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.52

Variant links:

Genes affected

SLC7A14 (HGNC:29326): (solute carrier family 7 member 14) This gene is predicted to encode a glycosylated, cationic amino acid transporter protein with 14 transmembrane domains. This gene is primarily expressed in skin fibroblasts, neural tissue, and primary endothelial cells and its protein is predicted to mediate lysosomal uptake of cationic amino acids. Mutations in this gene are associated with autosomal recessive retinitis pigmentosa. In mice, this gene is expressed in the photoreceptor layer of the retina where its expression increases over the course of retinal development and persists in the mature retina. [provided by RefSeq, Apr 2014]

SLC7A14 links:

ENSG00000285218 (HGNC:):

ENSG00000285218 links:

SLC7A14-AS1 (HGNC:54092): (SLC7A14 antisense RNA 1)

SLC7A14-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr3-170480891-C-A is described in Lovd as [Likely_pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.42392144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A14	NM_020949.3 link	c.1391G>C	p.Cys464Ser	missense_variant	7/8	ENST00000231706.6	NP_066000.2	Q8TBB6
SLC7A14-AS1	NR_135555.1 link	n.215+4018C>G		intron_variant
SLC7A14-AS1	NR_135556.1 link	n.215+4018C>G		intron_variant
SLC7A14-AS1	NR_135557.1 link	n.221+4018C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A14	ENST00000231706.6 link	c.1391G>C	p.Cys464Ser	missense_variant	7/8	2	NM_020949.3	ENSP00000231706.4		Q8TBB6
ENSG00000285218	ENST00000486975.1 link	c.391+57564C>G		intron_variant		2		ENSP00000417434.1		B4DFI2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.012

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.088

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.74

M_CAP

Benign

0.029

MetaRNN

Benign

0.42

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.090

REVEL

Uncertain

0.51

Sift

Benign

0.50

Sift4G

Benign

0.47

Polyphen

0.0050

Vest4

0.68

MutPred

0.48

Gain of glycosylation at C464 (P = 0.0162);

MVP

0.59

MPC

0.17

ClinPred

0.68

GERP RS

5.0

Varity_R

0.24

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over